Young women have much lower rates of cardiovascular disease (CVD, including stroke) than men. However, as midlife women transition to post-menopause, they lose this 'cardiovascular protection,'and CVD is most common in post-menopause than any other stage of a woman's lifespan. Metabolic Syndrome (MetS) is a clustering of 5 metabolic abnormalities and is a major predictor of CVD and type 2 diabetes. MetS is clinically diagnosed as having any, and at least, 3 of the 5 components. MetS occurrence increases during the menopausal transition (MT). Reasons for this are unclear;however this may be due to androgen excess, relative to estrogen, during the MT. The proposal's goal is to establish basic aspects of how the constellations of the MetS components evolve during the course of the MT, a key 5- to 10-year biological stage in a woman's lifespan. In turn, this is intended to identify customized ways of preventing MetS early and related CVD and diabetes, with effective intervention strategies during the MT. The proposal incorporates a shift in our thinking of menopause and sex hormones in midlife women, namely, that the increase in MetS occurrence may be due more to androgen gain (and less to estrogen loss), in the MT. Our starting hypothesis is that mapping the constellations of MetS components, and the number of MetS components satisfied, in the midlife will provide a window into bridging the MT, its changing sex hormones, and loss of CV protection in women. If correct, this would shift our clinical focus to individualize hormone strategies against characteristic MetS constellations and related CVD and diabetes in midlife and early post-menopausal women. Aim 1. To characterize the constellations of MetS components satisfied over time in women, of 5 race/ethnicities, who develop MetS as they undergo the MT. Aim 2. To determine the hormonal and inflammatory factors that predict the course of MetS constellations in midlife women as they undergo the MT. We propose an efficient study that analyzes unique, existing longitudinal data from the largest U.S. study of the MT, the Study of Women Across the Nation (SWAN), a multi-ethnic cohort of 3302 women. Our long-term objective is to prevent the dramatic increase in CVD in older women by implementing, in midlife, individualized preventative strategies. Both our aims bear directly on this wider objective. These would impact 60+ million midlife and older U.S. women. PUBLIC HEALTH RELEVANCE: The Metabolic Syndrome (MetS) is the major predictor for both CVD and type 2 diabetes, and can manifest as having one of several constellations of at least 3 of 5 risk components, such as high blood pressure and large waist girth. MetS occurs more often in women undergoing the menopausal transition, a key 5- to 10-year biological stage in a woman's lifespan. This study seeks to enhance significantly our understanding of how women in their 40s and early 50s, over time, develop MetS and hormonal changes and other factors during the menopausal transition that contribute to their increased risk of MetS. With this better understanding, we intend to ultimately prevent MetS in women who are high risk due to identifiable and modifiable characteristics of their transition to post-menopause. This potentially impacts tens of millions of midlife women and their families who face a nearly 1 in 3 chance of developing MetS in their remaining lifetime.